CKD Progression in Medicare Beneficiaries With Nonvalvular Atrial Fibrillation Treated With Apixaban Versus Warfarin

Abstract

Rationale & objective: Comparing kidney disease progression among patients treated with direct oral anticoagulants (DOACs) versus warfarin has not been well studied. We hypothesized that apixaban would be associated with lower risks of progression of chronic kidney disease (CKD) and progression to incident kidney failure than warfarin in patients with atrial fibrillation (AF).

Study design: Retrospective cohort study.

Setting & participants: Medicare recipients with stage 3, 4, or 5 CKD and incident AF who received a new prescription for apixaban or warfarin from 2013 through 2017.

Exposure: Apixaban or warfarin.

Outcomes: Progression to incident kidney failure or, separately, to a more advanced stage of CKD.

Analytical approach: Marginal structural cause-specific proportional hazards models with inverse probability weighting to estimate marginal hazard ratios (HRs) for each outcome. HRs compared apixaban to warfarin in intention-to-treat and censored-at-drug-switch analyses.

Results: 12,816 individuals met inclusion criteria (50.3% received apixaban; 49.7% received warfarin). After weighting, the mean age of the cohort was 80 ± 7 years, 51% were women, and 88% were White. Approximately 84% had stage 3, 15% had stage 4, and 1% had stage 5 CKD. In the intention-to-treat analysis, apixaban, relative to warfarin, was associated with an HR of developing incident kidney failure of 0.98 (95% confidence interval [CI], 0.79-1.22) and of CKD stage progression of 0.90 (95% CI, 0.82-0.99). Corresponding HRs for censored-at-drug-switch analyses were 0.81 (95% CI, 0.56-1.17) and 0.81 (95% CI, 0.70-0.92). Results were similar for a series of subgroup and sensitivity analyses.

Limitations: CKD was defined based on diagnosis codes from claims; findings may not be generalizable to non-Medicare CKD populations.

Conclusions: Apixaban, compared with warfarin, was associated with lower risk of CKD stage progression, but not with incident kidney failure.

Keywords: CKD progression; apixaban; atrial fibrillation (AF); chronic kidney disease (CKD); direct oral anticoagulants (DOACs); drug safety; end-stage renal disease (ESRD); ischemic stroke prevention; renal failure; warfarin.